Initiation of DNA replication is one of the most crucial events in the cell cycle, the elucidation of which is the key to the understanding and eventual treatment of many diseases, including cancers. We wish to address ourselves to the question of why protein and RNA syntheses are required for the initiation of each round of DNA replication. We are studying a special group of mutants (SdrC) of Escherichia coli in which the requirement for de novo protein synthesis appears to be circumvented. Our specific aims falls into three major studies. 1. Studies on the sdrA gene alleles. We propose to clone and sequence the sdrA+ gene, and identify the product of the sdrA+ gene. The susceptability of the sdrA+ gene product to recA protease will also be examined. 2. Studies on the role of recA+ protein in stable DNA replication. We propose to determine whether or not recA+ protein is required for initiatio of stable DNA replication in sdrA mutants. The rin mutations which are specific suppressors for the recA+ dependence of stable DNA replication will be characterized. 3. Isolation and characterization of SdrC mutants of F plasmid. Attempts will be made to isolate F sdr mutant (comparable to E. coli sdr mutants) with the expectation that F sdr mutants will simplify the analyisis of the problem.